1-(2-oxo-3-oxazolidinyl)-2-thiourea



United States Patent resented by the formula:

with a new chemical compound l(2-oxo-3-oxazolidinyl) 2-thiourea usefulin synthesis and represented by the formula:

and with processes for the preparation of these compounds.

The new compound of Formula I is distinguished by its chemotherapeuticactivity in the prevention and treatment of a broad spectrum ofparasitic infections in poultry and animals when administered in farless than toxic amount. Protozoan diseases in poultry provoked byorganisms such as H istomonas meleagridis and Eimeria tenella areeffectively combatted by the administration in the feed supply of fromabout 0.0l1-0.022% by Weight of this compound. Bacterial infections arereadily susceptible to this new compound; for instance, mice lethallyinfected by Staphylococcus aareus or Salmonella typhosa are protectedfrom death by the oral administration of as little as 105 mg./kg.Trypanosome infections also yield to this compound; for instance, miceinfected with Trypanosoma foetus are ridded of this organism by the oraladministration of dosages of about 30 mg./kg. over a four-day period.Helminthic infections are similarly susceptible to treatment with thiscompound; for instance, mice harboring Syphacia obvelata are relieved byadministration b.i.d. of 50 mg./ kg. for four days.

This compound is relatively non-toxic. In mice the highest tolerateddose of it is greater than 1000 mg./kg. Its administration at a level of0.022% in the diet of turkeys and chickens has manifested no sign oftoxic effect.

The broad antimicrobial therapeutic effectiveness and low toxicity ofthis compound makes it a valuable medicinal agent.

The new compound represented by Formula II is useful in synthesis. It isvaluable as an intermediate in the production of the compound of FormulaI. In accordance with this invention it is readily prepared by reacting3-amino-2-oxazolidone with an alkali thiocyanate such as ice potassiumthiocyanate and in an aqueous medium and in the presence of a mineralacid such as hydrochloric. To facilitate its preparation, heat may besupplied to the reaction mixture. The product 1- (2-oxo-3-oxazolidinyl)-2-thiourea is readily recovered by cooling and filtering the reactionmixture.

The compound represented by Formula I is readily prepared by bringingtogether a halomethyl 5-nitro-2-furyl ketone and the compoundrepresented by Formula II. In accordance with this invention, theprocess currently preferred consists in mixing bromoethyl5-nitro-2-furyl ketone and 1-(2-oxo-3-oxazolidinyl)-2-thiourea in aninert medium such as ethanol and heating until reaction is complete. Itis advantageous to stir the reaction mixture to bring about gooddispersion and contact of the reactants. The reaction mixture is cooledand the product filtered. It may be recrystallized from a suitablesolvent such as ethanol, if desired.

The compound represented by Formula I can be compounded in variouspharmaceutical forms such as tablets, capsules, suspensions, troches,and the like using eXcipients and adjuvants common to the art ofpharmacy. When used in the veterinary field a convenient form ofadministration is through admixture in the feed supply.

In order that this invention may be readily available to and understoodby those skilled in the art, the following examples are given:

EXAMPLE I 1-(2-Ox0-3-0xaz0lidinyl) -2-Thi0urea A solution of3-amino-2-oxazolidone (60 g., 0.6 mole) and potassium thiocyanate g.,0.67 mole) in ml. of water is treated with 50 ml. of concentratedhydrochloric acid and heated on the steam bath for 1 /2 hours. Aftercooling, the solid (72.5 g.) is filtered. It may be recrystallized from1380 ml. of Water. The yield of pure material is 62 g. (64%); M.P.195-196".

EXAMPLE II 3- [4- (5 -Nitr0-2-F uryl -2-Thiaz0lylamin0] -2-Oxaz0lidinoneA mixture of 46.8 g. (0.2 mole) of bromomethyl S-nitro-Z-furyl ketoneand 32.2 g. (0.2 mole) of 1-(2-oxo- 3-oxazolidinyl)-2-thiourea in 500ml. of alcohol is refluxed for 1 hour with stirring. After cooling, theyellow solid (53.2 g., M.P. 165) is filtered and recrystallized from1600 ml. of alcohol. The yield of 3-[4-(5-nitro-2- furyl) 2thiazolylamino] 2 oxazolidinone is 45.3 g. (77%); M.P. -173".

Many other equivalent modifications will be apparent to those skilled inthe art from a reading of the above without a departure from theinventive concept.

This application is a division of application S.N. 93,883, filed March7, 1961.

What is claimed is:

The compound 1-(2-oxo 3 oxazolidinyl)-2-thiourea represented by theformula:

HzNCSNHNC=O 0 HzC-Cfig No references cited.

